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Complex Solutions in Modular Design
- Dr Thomas Brinz, Director, Lab Systems and Custom Solutions, Bosch Packaging Technology
Laboratory automation has significantly changed chemical and pharmaceutical research since the 1980s. Complex automation and handling solutions have proven successful in chemical laboratories for a long time. This concept of lab automation and handling is now being transferred to the pharmaceutical market.

Mixing, stirring, dosing, applying regardless of the outcome, a machine maps certain processes. These may lead to the production of varnishes, pesticides, glues, or pharmaceutical formulations. The pharmaceutical industry can learn and benefit from these kinds of procedures and systems, which have already been successful in chemistry for some time. As pharmaceutical laboratories continuously automate their processes, the need for individual solutions and complex special-purpose machinery is also on the rise. The aim is to transfer customised development processes into industry-standard, highly flexible and modular automation solutions for the pharmaceutical market – from fundamental research to product and quality control.

Higher Throughput, Faster Product Development
Over many decades, chemical and pharmaceutical laboratory technicians have developed samples in numerous manual trials. Methods from combinatorial chemistry triggered major changes, which are especially important for the development of new medicines. Automation has simplified processing operations and significantly increased the reproducibility of trial results. Automated processes and experiments can now be carried out simultaneously. They can also be repeated as often as required with comparatively small effort. This leads to a significant improvement of results.

Automated laboratory procedures give users access to a wide spectrum of processes and analytical opportunities. Thanks to the large amount of available samples, automated processes now lead to the final product much quicker. Moreover they considerably reduce the use of raw material. Solutions for lab automation such as Bosch’s system for “high-throughput synthesis and screening” quickly lead to higher performance. In the chemical industry, automation increases lab efficiency by a factor of approximately 2.5. This corresponds to a reduction of 60 per cent in terms of time and costs. The automated lab offers a further important advantage: Useful reactions and process parameters are often not found by manual formulation tests. The manual lab classifies some additives as ‘not exploitable’ and eliminates them. However, automated test series reveal how useful these additives are in combination with other compounds, for example when testing the solubility of active substances.

New Patented Formulation Technology
The patented BLS (Bosch Lab Systems) syringe was originally developed by Bosch for the chemical industry. But it also promises great improvements to pharmaceutical labs: Together with the powder formulation, also patented by Bosch, it forms the basis for the formulation technology. In both chemistry and pharmacy, liquids with different viscosities, pigments and additives serve as raw materials for the mixture.

Traditional dosing technologies apply these liquids by sucking in the material. However, they do not process media with high viscosity. The patented BLS syringe greatly facilitates this procedure, because its cylinder can absorb media with different textures. By using a piston with separate outflow, the syringe becomes a very precise dosing device.

Raw material container and reaction process vessel are both integrated in the airlessly filled syringe. The same syringe can be used for developing and applying formulations in order to test the properties under realistic conditions. This enables the production of highly complex formulations such as oil/water emulsions. The disposable syringe not only eliminates cleaning efforts. It also significantly reduces the amount of liquid waste.

Modules Flexibly Combined
Larger machines make handling a lot easier. By moving along the linear axis, handling robots carry out highly complex actions. The robots are adapted to customers’ needs with a combination of standardised and flexible modules. The technological foundation of these modular combinations is key for their flexibility: based on a modular construction system, the required components are connected with each other to form customised solutions. This modular concept enables to offer complex special constructions, combining different assembly groups along the value chain. They range from fundamental research to quality control, and include the integration of external customer-owned processes.

Focusing on the Pharmaceutical Industry
Over the last years, this lab automation concept has been successfully implemented in the chemical industry many times. For example, Bosch cooperated with BASF in the development of high-throughput screening equipment for varnish. Up to 100 different types of varnish systems can be processed within a very short time. Considering the broad range of varnish systems that needed to be examined, Bosch’s BLS syringe dosing system was the key to success. The system was awarded the ‘Farbe und Lack Preis’ for its environmental friendliness in 2005.

These achievements have now also entered the pharmaceutical market: “The pharmaceutical industry focuses on the medicinal and chemical design of small molecules and their biological testing for active ingredient research.

We use automated systems to replace the traditional manual and repetitive tasks in chemical synthesis, filtration or analytics by new processes and innovative technologies,” said Stefan Oberbörsch, Head of Medicinal Chemistry Technologies at Grünenthal GmbH in Aachen, Germany. Another user of these specific solutions from Bosch is Eurofins MWG Operon, headquartered in Ebersberg near Munich, provider of services for DNA, RNA and gen syntheses as well as sequencing, applied genetics and forensics. The company uses a robot for storing and sending DNA samples.